Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF)
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Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF). / Jacobsen, Jens C.B.; Schubert, Irene H.; Larsen, Karin; Terzic, Dijana; Thisted, Louise; Thomsen, Morten B.
I: Acta Physiologica, Bind 240, Nr. 3, e14099, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF)
AU - Jacobsen, Jens C.B.
AU - Schubert, Irene H.
AU - Larsen, Karin
AU - Terzic, Dijana
AU - Thisted, Louise
AU - Thomsen, Morten B.
N1 - Publisher Copyright: © 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.
PY - 2024
Y1 - 2024
N2 - Aim: Heart Failure with preserved Ejection Fraction (HFpEF) is characterized by diastolic dysfunction and reduced cardiac output, but its pathophysiology remains poorly understood. Animal models of HFpEF are challenging due to difficulties in assessing the degree of heart failure in small animals. This study aimed at inducing HFpEF in a mouse model to probe preload-dependency. Methods: Increased body mass and arterial hypertension were induced in mice using a Western diet and NO synthase inhibition. Preload dependence was tested ex vivo. Results: Mice with obesity and hypertension exhibited reduced cardiac output, indicating a failing heart. Increased left ventricular filling pressure during diastole suggested reduced compliance. Notably, the ejection fraction was preserved, suggesting the development of HFpEF. Spontaneous physical activity at night was reduced in HFpEF mice, indicating exercise intolerance; however, the cardiac connective tissue content was comparable between HFpEF and control mice. The HFpEF mice showed increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for the rigid left ventricle, preventing a critical decrease in cardiac output. Conclusion: This animal model successfully developed mild HFpEF with a reduced pump function that was dependent on a high preload. A model of mild HFpEF may serve as a valuable tool for studying disease progression and interventions aimed at delaying or reversing symptom advancement, considering the slow development of HFpEF in patients.
AB - Aim: Heart Failure with preserved Ejection Fraction (HFpEF) is characterized by diastolic dysfunction and reduced cardiac output, but its pathophysiology remains poorly understood. Animal models of HFpEF are challenging due to difficulties in assessing the degree of heart failure in small animals. This study aimed at inducing HFpEF in a mouse model to probe preload-dependency. Methods: Increased body mass and arterial hypertension were induced in mice using a Western diet and NO synthase inhibition. Preload dependence was tested ex vivo. Results: Mice with obesity and hypertension exhibited reduced cardiac output, indicating a failing heart. Increased left ventricular filling pressure during diastole suggested reduced compliance. Notably, the ejection fraction was preserved, suggesting the development of HFpEF. Spontaneous physical activity at night was reduced in HFpEF mice, indicating exercise intolerance; however, the cardiac connective tissue content was comparable between HFpEF and control mice. The HFpEF mice showed increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for the rigid left ventricle, preventing a critical decrease in cardiac output. Conclusion: This animal model successfully developed mild HFpEF with a reduced pump function that was dependent on a high preload. A model of mild HFpEF may serve as a valuable tool for studying disease progression and interventions aimed at delaying or reversing symptom advancement, considering the slow development of HFpEF in patients.
KW - compliance
KW - diastolic dysfunction
KW - fibrosis
KW - heart failure
KW - high-fat diet
KW - L-NAME
KW - obesity
U2 - 10.1111/apha.14099
DO - 10.1111/apha.14099
M3 - Journal article
C2 - 38230889
AN - SCOPUS:85182448950
VL - 240
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 3
M1 - e14099
ER -
ID: 381068620